The multi-epitope polypeptide approach in HIV-1 vaccine development

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Developing countries urgently need a preventive HIV vaccine to combat the AIDS pandemic.
• Cuban institutions have pursued HIV vaccine development since 1992, focusing on multi-epitope polypeptides (MEPs) and cytotoxic T cell (CTL) responses.
• This article details progress on the MEP strategy for HIV vaccine development.

Purpose of the Study:

• To construct and evaluate the immunogenicity of recombinant multi-epitope polypeptides (MEPs) based on HIV-1 V3 loop sequences.
• To select a promising MEP candidate for a Phase I clinical trial.
• To assess the safety and immunogenicity of the selected MEP vaccine in human volunteers.

Main Methods:

• MEPs were designed incorporating V3 loop epitopes from various HIV-1 isolates.
• Immunogenicity was assessed in preclinical models (mice, rabbits, macaques).
• A Phase I clinical trial utilized the selected MEP (TAB9) with Montanide ISA720 adjuvant in HIV-seronegative volunteers, employing a double-blind, randomized design.

Main Results:

• The MEP TAB9, containing six V3 epitopes, was chosen for clinical evaluation.
• All vaccinated volunteers exhibited a robust immune response.
• Neutralizing antibodies were detected in 50% of participants; however, severe local reactions occurred after subsequent inoculations.

Conclusions:

• The TAB9 MEP vaccine formulation demonstrated immunogenicity and induced neutralizing antibodies in a portion of the trial participants.
• Safety concerns, specifically severe local reactions, were identified during the Phase I trial.
• A new formulation of TAB9 is under preclinical development to address tolerability issues before further clinical trials.